A number of treatments and compositions for topical application are promoted in the art for mitigating dermatological conditions of the skin which frequently are associated with natural or environmental causes, such as the process of aging (i.e., intrinsic aging), exposure to the sun, or the resulting ultraviolet radiation therefrom (i.e., extrinsic aging), and the like. Other factors, such as improper care and/or diet, stress, nutritional deficiencies, repeated facial movement and genetic predisposition also contribute to the development of adverse skin conditions, such as fine lines, frown lines, folds, furrows and wrinkles.
Popular culture and trends, the fashion industry, and many arms of the current media promote and encourage a youthful appearance that reflects skin, particularly facial skin, which is free of wrinkles, fine lines and the like. In today's world, both women and men desire to maintain a youthful, wrinkle-free appearance for as long as possible and consequently seek to prevent, reduce, improve, or eliminate the signs of aging (and/or sun exposure) which reveal themselves in the forms of fine lines, furrows, and wrinkles, for example. The products commonly available to date for this purpose typically contain agents that act on the skin by merely moisturizing, promoting cell growth, swelling the extracellular matrix (by, for example, increasing or promoting the synthesis of collagen, elastin or glycosaminoglycans) which comprises skin. Calcium channel inhibitory agents that act on calcium channels of subcutaneous muscle and/or nerve tissue have also been described as components of compositions to relax and/or decontract cutaneous and/or subcutaneous tissue whose contraction is associated with wrinkle formation (U.S. Pat. No. 6,344,461 B1 to L. Breton et al.).
Compositions containing active agents and ingredients for use in personal care products to affect, prevent, and/or reduce hyperhidrosis, such as antiperspirants and deodorants, are also widely employed in the general population. Such compositions are provided to reduce and prevent perspiration and body malodor associated with human perspiration and sweating, particularly underarm malodor, and ideally should contain constituents that are effective in the treatment of sweating following topical application to the skin. While antiperspirants combat auxiliary body malodors by inhibiting perspiration through, for example, the action of astringent salts such as aluminum and zirconium salts, deodorants neutralize objectionable odors resulting from the degradation of the components of sweat which are attacked by chemicals and microbes, thereby producing foul-smelling fatty acids.
By the regular use of antiperspirants or deodorants, a considerable number of users have experienced pain and/or irritation in the sensitive skin or body surface to which the antiperspirant or deodorant is applied, due to the active salts in these compositions, as well as to skin sensitivity. As is appreciated by the practitioner, deodorants are generally less irritating to the skin than antiperspirants because deodorants do not inhibit sweat, but rather neutralize the degradation products of sweat. Despite this, however, deodorants can also be irritating to sensitive skin, particularly for those whose skin is compromised in certain areas (e.g., the underarm area) as a result of shaving. Also, deodorants are difficult to use in other sweat-prone areas (e.g., feet, palms, groin). In view of the widespread use of such personal care products, effective antiperspirant and deodorant compositions are desired to inhibit, prevent, or reduce perspiration and body malodor with less irritation to the body and skin of the user.
Many of the compositions described for various topical treatments of the skin include components, such as alpha-hydroxyacids (“AHAs”), that may provide only superficial effectiveness, or that may cause adverse side effects to the user's skin, for example, irritation. Indeed, some commonly used compositions and methods for reducing fine lines and/or wrinkles contain AHAs, such as glycolic acid, lactic acid, tartaric acid and citric acid, and salts thereof, or they contain tretinoin, also known as all-trans retinoic acid or retinol (Vitamin A), or ascorbic acid (Vitamin C), all of which, without further mitigation, can induce the above-mentioned disadvantageous effects, often due to a lowering of the pH of the skin, among other factors. To provide maximum effectiveness and to avoid or prevent the foregoing types of adverse reactions, new and alternative components of compositions and formulations for the treatment and care of the skin are desired.
Human skin comprises two major compartments: a superficial outer compartment, the epidermis, and a deeper compartment, the dermis. The outermost epidermal skin layers typically provide a certain degree of protection to the body, although fine lines and wrinkles can be readily visualized in this portion of the skin. The epidermis and dermis bear the brunt of harmful effects of photodamage. The natural human epidermis functions to provide the essential protectant role of the skin in the human body. The dermis, which provides a solid and nutritional support to the epidermis, comprises mainly fibroblasts and an extracellular matrix composed primarily of a substance that includes collagen, elastin and glycosaminoglycans (“GAGs”). In addition, the dermis contains leukocytes, mast cells, tissue macrophages, blood vessels, muscle cells and nerve fibers.
The dermal muscles of the face are controlled by motor nerve afferences of the facial nerve. The interlobular septa of the hypoderm contain within them fibers that constitute a striated muscle tissue, i.e., the panniculus carnosus. It is known that a subpopulation of dermal fibroblasts, called myofibroblasts, has contractile characteristics similar to those of muscle cells and tissue.
Botulinum toxin, (also known by the trade name, Botox®, Allergen, Irvine, Calif.), is currently in vogue for treating wrinkles and fine lines, but was initially used to treat spasms. This toxin acts on states of muscular spasticity by specifically inhibiting neurotransmission in nerve cells, thereby causing contracted muscles to relax (e.g., A. Blitzer et al., 1993, Arch. Otolaryngol. Head Neck Surg., 119:118-122; U.S. Pat. No. 6,344,461 B1 to L. Breton et al.). Botulinum toxin also can act on wrinkles of the glabella (wrinkles between the eyebrows) when injected subcutaneously. (See, J. D. Carruthers, 1992, J. Dermatol. Surg. Oncol., 18:17-21; U.S. Pat. No. 6,344,461 B1 to L. Breton et al.). However, the full extent of adverse effects related to long-term use of botulinum toxin and products or treatments containing this material are still not well established. Botulinum toxin treatment has been associated with a number of side effects including, transient fatigue, dysphagia, neck weakness, hoarseness, and localized pain. In addition, many patients who preliminarily respond to botulinum toxin subsequently become non-responsive to treatment. (See, e.g., published U.S. Patent Application No. US2002/00812914 to Hawrot).
New ingredients for use as effective, active agents in compositions and formulations for application, preferably topical application, to the skin are advantageous to the industry and the consumer for a variety of uses in the areas of skin care treatment and therapy, and personal use products.
Plant extracts and substances serving a variety of diverse purposes include limonoid constituents of the Maliaecae and Rutaceae families. Limonoids are a group of chemically related triterpene derivatives which are among the bitter principles found in citrus fruits such as lemons, lime, orange and grapefruit. They are also present as glucose derivatives in mature fruit tissues and seeds, and are one of the major secondary metabolites present in citrus. More specific examples of such plant materials include the plant alkaloids toosendan (from Melia Toosendan Sieb. Et. Zucc), (i.e., Chinaberry) and azadirachtin (from Melia Azadirachta (i.e., Neem). Limonoids have been known to have insecticidal properties (e.g., U.S. Pat. No. 6,372,239 to Wu et al.; U.S. Pat. No. 5,885,600 to M. Blum et al.), as well as anti-neoplastic and anti-carcinogenic effects in laboratory animals (e.g., U.S. Pat. No. 5,370,873 to I. J. Udeinya; U.S. Pat. Nos. 6,239,114 and 6,251,400 to N. Guthrie et al.). The furan moiety attached to the D-ring is specifically responsible for detoxifying the chemical carcinogen glutathione-S-transferase enzyme system (Lam et al., 1994, Food Technology, 48:104-108).
Citrus fruit tissues and the byproducts of juice processing, such as peels and molasses are sources of limonoid glucosides and citrus seeds contain high concentrations of both limonoid aglycones and glucosides. Limonoid aglycones in the fruit tissues gradually disappear during the late stages of fruit growth and maturation. Thirty-eight limonoid aglycones have been isolated from citrus. The limonoids are present in three different forms, namely, the dilactone is present as the open D-ring form (monolactone), the limonoate A-ring lactone and the glucoside form (See, e.g., U.S. Pat. No. 6,239,114 to N. Guthrie et al.). Only the monolactones and glucosides are present in fruit tissues. (Hasegawa S. et al., 1994, In: Food Phytochemicals for Cancer Prevention I, Eds M-T. Huang et al, American Chemical Society, 198-207).
Procedures for the extraction and isolation of both aglycones and glucosides have been established to obtain concentrated sources of various limonoids (Lam, L. K. T. et al., 1994, In: Food Phytochemicals for Cancer Prevention, Eds. M. Huang, T. Osawa, C. Ho and R. T. Rosen, ACS Symposium Series 546, p 209).
Safe, effective and new components of compositions to treat, prevent, reduce, inhibit, and/or improve the dermatological signs of aging, as well as hyperhidrosis, would be advantageous for the formulation of treatments and products for the skin. As described herein, novel and beneficial methods and compositions, as well as their mode of action, for the treatment of wrinkles and the like, as well as for personal care products for the skin, are provided by the present invention.